Background For lung adenocarcinoma patients with epidermal growth factor receptor (EGFR) sensitive mutation and synchronous brain metastasis (syn‐BM), when and how to apply radiotherapy (RT) during first‐line tyrosine kinase inhibitor (TKI) treatment remains debatable. Methods From a real‐world multicenter database, EGFR‐mutant patients with syn‐BM diagnosed between 2010–2020 and treated with first‐line TKIs were enrolled and divided into upfront TKI + RT and upfront TKI groups. Median intracranial progression‐free survival (mIC‐PFS), median overall survival (mOS), and their risk factors were estimated. Results There were 60 and 186 patients in the upfront TKI + RT group and upfront TKI group, respectively. Their mIC‐PFS were 28.9 months (m) and 17.5 m (p = 0.023), and mOS were 42.7 m and 40.1 m (p = 0.51). Upfront brain RT improved mIC‐PFS in patients ≤60‐year‐old (p = 0.035), with symptomatic BM (p = 0.002), and treated with first‐generation TKIs (p = 0.012). There was no significant difference in mOS in any subgroup. Upfront brain stereotactic radiosurgery (SRS) showed a trend of better mIC‐PFS and mOS. mIC‐PFS was independently correlated with symptomatic BM (HR = 1.54, p = 0.030), EGFR L858R mutation (HR = 1.57, p = 0.019), and upfront brain RT (HR = 0.47, p = 0.001). mOS was independently correlated with being female (HR = 0.54, p = 0.007), ECOG 3–4 (HR = 10.47, p 3 (HR = 2.19, p = 0.002), and third‐generation TKI (HR = 0.54, p = 0.044) or antiangiogenic drugs (HR = 0.11, p = 0.005) as first/second‐line therapy. Conclusions Upfront brain RT based on first‐line EGFR‐TKI might improve IC‐PFS but not OS in EGFR‐mutant lung adenocarcinoma patients, indicating potential survival benefit from brain SRS and early application of drugs with higher intracranial activity.
To our best knowledge, this is the most extensive multicenter real‐world study (Fig.1) on epidermal growth factor receptor (EGFR) mutant lung adenocarcinoma with synchronous brain metastasis (BM) and treated with first‐line EGFR targeting tyrosine kinase inhibitor (TKI). On the basis of first‐line EGFR‐TKI therapy, additional upfront brain radiation therapy (RT) could improve intracranial progression free survival (PFS) (Fig.2a), particularly for patients with BM symptom and 1st‐generation EGFR‐TKI (Fig.4a). With no OS improvement (Fig.2d, Fig.3b, Fig.4b), upfront whole‐brain irradiation could be deferred during the first‐line EGFR‐TKI treatment; however, upfront brain stereotactic radio‐surgery (SRS) might have potential OS benefit (Fig.3d).